AU2004239338A1 - GRP94-based compositions and methods of use thereof - Google Patents
GRP94-based compositions and methods of use thereof Download PDFInfo
- Publication number
- AU2004239338A1 AU2004239338A1 AU2004239338A AU2004239338A AU2004239338A1 AU 2004239338 A1 AU2004239338 A1 AU 2004239338A1 AU 2004239338 A AU2004239338 A AU 2004239338A AU 2004239338 A AU2004239338 A AU 2004239338A AU 2004239338 A1 AU2004239338 A1 AU 2004239338A1
- Authority
- AU
- Australia
- Prior art keywords
- grp94
- peptide
- protein
- cells
- binding
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108010017007 glucose-regulated proteins Proteins 0.000 title claims description 441
- 238000000034 method Methods 0.000 title claims description 98
- 102100039328 Endoplasmin Human genes 0.000 title claims description 20
- 239000000203 mixture Substances 0.000 title claims description 17
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 409
- 108090000623 proteins and genes Proteins 0.000 claims description 264
- 210000004027 cell Anatomy 0.000 claims description 236
- 102000004169 proteins and genes Human genes 0.000 claims description 215
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 169
- 210000002257 embryonic structure Anatomy 0.000 claims description 110
- 206010028980 Neoplasm Diseases 0.000 claims description 94
- 150000007523 nucleic acids Chemical class 0.000 claims description 90
- 102000039446 nucleic acids Human genes 0.000 claims description 84
- 108020004707 nucleic acids Proteins 0.000 claims description 84
- 150000001413 amino acids Chemical class 0.000 claims description 70
- 230000000694 effects Effects 0.000 claims description 61
- 108010006519 Molecular Chaperones Proteins 0.000 claims description 60
- 101710113864 Heat shock protein 90 Proteins 0.000 claims description 44
- 230000002950 deficient Effects 0.000 claims description 38
- 239000000427 antigen Substances 0.000 claims description 37
- 108091007433 antigens Proteins 0.000 claims description 37
- 102000036639 antigens Human genes 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 31
- 102000005431 Molecular Chaperones Human genes 0.000 claims description 28
- 210000001161 mammalian embryo Anatomy 0.000 claims description 28
- 230000004044 response Effects 0.000 claims description 27
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 23
- 201000011510 cancer Diseases 0.000 claims description 21
- 230000035772 mutation Effects 0.000 claims description 21
- 230000028993 immune response Effects 0.000 claims description 20
- 241000700605 Viruses Species 0.000 claims description 19
- 238000012360 testing method Methods 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 17
- 230000004075 alteration Effects 0.000 claims description 14
- 125000000539 amino acid group Chemical group 0.000 claims description 14
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 12
- 238000011830 transgenic mouse model Methods 0.000 claims description 12
- 238000012216 screening Methods 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 210000004698 lymphocyte Anatomy 0.000 claims description 10
- 230000036210 malignancy Effects 0.000 claims description 9
- 230000009467 reduction Effects 0.000 claims description 9
- 230000004936 stimulating effect Effects 0.000 claims description 9
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 8
- 108010022937 endoplasmin Proteins 0.000 claims description 8
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims description 7
- 208000015181 infectious disease Diseases 0.000 claims description 7
- 230000003612 virological effect Effects 0.000 claims description 7
- 208000036142 Viral infection Diseases 0.000 claims description 5
- 210000001789 adipocyte Anatomy 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 230000009385 viral infection Effects 0.000 claims description 5
- 230000024245 cell differentiation Effects 0.000 claims description 4
- 239000013604 expression vector Substances 0.000 claims description 4
- 210000003494 hepatocyte Anatomy 0.000 claims description 4
- 210000002569 neuron Anatomy 0.000 claims description 4
- 230000035790 physiological processes and functions Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000002744 homologous recombination Methods 0.000 claims description 3
- 230000006801 homologous recombination Effects 0.000 claims description 3
- 238000011534 incubation Methods 0.000 claims description 3
- 238000000520 microinjection Methods 0.000 claims description 3
- CSHFHJNMIMPJST-HOTGVXAUSA-N methyl (2s)-2-[[(2s)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoate Chemical compound NCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)OC)CC1=CC=CC=C1 CSHFHJNMIMPJST-HOTGVXAUSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 210000000472 morula Anatomy 0.000 claims 1
- 230000027455 binding Effects 0.000 description 243
- 238000009739 binding Methods 0.000 description 225
- 235000018102 proteins Nutrition 0.000 description 206
- 230000014509 gene expression Effects 0.000 description 91
- 229920001184 polypeptide Polymers 0.000 description 73
- AECPBJMOGBFQDN-YMYQVXQQSA-N radicicol Chemical compound C1CCCC(=O)C[C@H]2[C@H](Cl)C(=O)CC(=O)[C@H]2C(=O)O[C@H](C)C[C@H]2O[C@@H]21 AECPBJMOGBFQDN-YMYQVXQQSA-N 0.000 description 72
- VYGYNVZNSSTDLJ-HKCOAVLJSA-N monorden Natural products CC1CC2OC2C=C/C=C/C(=O)CC3C(C(=CC(=C3Cl)O)O)C(=O)O1 VYGYNVZNSSTDLJ-HKCOAVLJSA-N 0.000 description 70
- 229930192524 radicicol Natural products 0.000 description 70
- 235000001014 amino acid Nutrition 0.000 description 66
- 239000012634 fragment Substances 0.000 description 46
- 239000000523 sample Substances 0.000 description 41
- 108020004414 DNA Proteins 0.000 description 39
- 241000699666 Mus <mouse, genus> Species 0.000 description 34
- 241000699670 Mus sp. Species 0.000 description 34
- HMWAJFNEGAJETK-UHFFFAOYSA-N 1-[6-(dimethylamino)naphthalen-2-yl]prop-2-en-1-one Chemical compound C1=C(C(=O)C=C)C=CC2=CC(N(C)C)=CC=C21 HMWAJFNEGAJETK-UHFFFAOYSA-N 0.000 description 29
- 210000001744 T-lymphocyte Anatomy 0.000 description 29
- FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 29
- 238000009396 hybridization Methods 0.000 description 29
- 210000003716 mesoderm Anatomy 0.000 description 29
- 230000002209 hydrophobic effect Effects 0.000 description 28
- 101100011744 Dictyostelium discoideum grp94 gene Proteins 0.000 description 27
- 238000012986 modification Methods 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 230000004048 modification Effects 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 25
- 238000011161 development Methods 0.000 description 25
- 230000018109 developmental process Effects 0.000 description 25
- 210000001519 tissue Anatomy 0.000 description 24
- 239000013598 vector Substances 0.000 description 23
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 22
- 230000006870 function Effects 0.000 description 22
- 239000003112 inhibitor Substances 0.000 description 22
- 239000002773 nucleotide Substances 0.000 description 22
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
- 125000003729 nucleotide group Chemical group 0.000 description 21
- 241001465754 Metazoa Species 0.000 description 20
- 108091034117 Oligonucleotide Proteins 0.000 description 20
- 238000013459 approach Methods 0.000 description 20
- 238000003556 assay Methods 0.000 description 20
- 230000004069 differentiation Effects 0.000 description 20
- 230000003993 interaction Effects 0.000 description 20
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 19
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 19
- 125000003275 alpha amino acid group Chemical group 0.000 description 19
- 230000000295 complement effect Effects 0.000 description 19
- 230000006698 induction Effects 0.000 description 19
- 239000013615 primer Substances 0.000 description 19
- 230000008685 targeting Effects 0.000 description 18
- 241001529936 Murinae Species 0.000 description 17
- 230000002068 genetic effect Effects 0.000 description 17
- 239000003446 ligand Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 16
- 238000002474 experimental method Methods 0.000 description 16
- 210000001811 primitive streak Anatomy 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 108700028369 Alleles Proteins 0.000 description 15
- 239000000872 buffer Substances 0.000 description 15
- 230000008859 change Effects 0.000 description 15
- 210000001900 endoderm Anatomy 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 230000001105 regulatory effect Effects 0.000 description 15
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 14
- 108091054437 MHC class I family Proteins 0.000 description 14
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 14
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 210000003719 b-lymphocyte Anatomy 0.000 description 14
- 230000007547 defect Effects 0.000 description 14
- 210000004443 dendritic cell Anatomy 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 230000007045 gastrulation Effects 0.000 description 14
- 239000008103 glucose Substances 0.000 description 14
- 238000000338 in vitro Methods 0.000 description 14
- 108010091748 peptide A Proteins 0.000 description 14
- 238000003752 polymerase chain reaction Methods 0.000 description 14
- 210000002966 serum Anatomy 0.000 description 14
- 238000007792 addition Methods 0.000 description 13
- 210000000612 antigen-presenting cell Anatomy 0.000 description 13
- 230000004071 biological effect Effects 0.000 description 13
- 239000002299 complementary DNA Substances 0.000 description 13
- 210000000987 immune system Anatomy 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 239000003550 marker Substances 0.000 description 13
- 230000009278 visceral effect Effects 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 12
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 12
- 210000001654 germ layer Anatomy 0.000 description 12
- 230000012010 growth Effects 0.000 description 12
- 125000000487 histidyl group Chemical class [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 12
- 238000003032 molecular docking Methods 0.000 description 12
- 230000036961 partial effect Effects 0.000 description 12
- 238000000159 protein binding assay Methods 0.000 description 12
- 230000035882 stress Effects 0.000 description 12
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 11
- 102000043129 MHC class I family Human genes 0.000 description 11
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 11
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 11
- 239000011230 binding agent Substances 0.000 description 11
- 210000003981 ectoderm Anatomy 0.000 description 11
- 239000000499 gel Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 210000004899 c-terminal region Anatomy 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 230000013020 embryo development Effects 0.000 description 10
- 239000002158 endotoxin Substances 0.000 description 10
- 235000014304 histidine Nutrition 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 229920006008 lipopolysaccharide Polymers 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 239000000758 substrate Substances 0.000 description 10
- 102000053602 DNA Human genes 0.000 description 9
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 9
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 9
- 101150112743 HSPA5 gene Proteins 0.000 description 9
- 101150065069 Hsp90b1 gene Proteins 0.000 description 9
- 101100445364 Mus musculus Eomes gene Proteins 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 101100111629 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR2 gene Proteins 0.000 description 9
- 101100445365 Xenopus laevis eomes gene Proteins 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 101150028578 grp78 gene Proteins 0.000 description 9
- 238000003780 insertion Methods 0.000 description 9
- 230000037431 insertion Effects 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- 230000035755 proliferation Effects 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- 108090000190 Thrombin Proteins 0.000 description 8
- 241000711975 Vesicular stomatitis virus Species 0.000 description 8
- 230000000890 antigenic effect Effects 0.000 description 8
- 210000002459 blastocyst Anatomy 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 230000028327 secretion Effects 0.000 description 8
- 229960004072 thrombin Drugs 0.000 description 8
- 108091026890 Coding region Proteins 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 230000033228 biological regulation Effects 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 210000004039 endoderm cell Anatomy 0.000 description 7
- 238000007901 in situ hybridization Methods 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 230000035945 sensitivity Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 238000012546 transfer Methods 0.000 description 7
- 230000009261 transgenic effect Effects 0.000 description 7
- 108010094106 vesicular stomatitis virus nucleoprotein (52-59) Proteins 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- 108020004635 Complementary DNA Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- 108010074860 Factor Xa Proteins 0.000 description 6
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 description 6
- 108091023040 Transcription factor Proteins 0.000 description 6
- 102000040945 Transcription factor Human genes 0.000 description 6
- 230000030741 antigen processing and presentation Effects 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
- -1 co-factors Substances 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 230000029087 digestion Effects 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 239000006166 lysate Substances 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 210000004962 mammalian cell Anatomy 0.000 description 6
- 230000008774 maternal effect Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 230000006798 recombination Effects 0.000 description 6
- 238000005215 recombination Methods 0.000 description 6
- 230000003248 secreting effect Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- IXFPJGBNCFXKPI-FSIHEZPISA-N thapsigargin Chemical compound CCCC(=O)O[C@H]1C[C@](C)(OC(C)=O)[C@H]2[C@H](OC(=O)CCCCCCC)[C@@H](OC(=O)C(\C)=C/C)C(C)=C2[C@@H]2OC(=O)[C@@](C)(O)[C@]21O IXFPJGBNCFXKPI-FSIHEZPISA-N 0.000 description 6
- 230000014616 translation Effects 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 5
- 230000005867 T cell response Effects 0.000 description 5
- 102000002689 Toll-like receptor Human genes 0.000 description 5
- 108020000411 Toll-like receptor Proteins 0.000 description 5
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 5
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 5
- 238000002679 ablation Methods 0.000 description 5
- 230000000692 anti-sense effect Effects 0.000 description 5
- 101150067309 bmp4 gene Proteins 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 238000007877 drug screening Methods 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 102000037865 fusion proteins Human genes 0.000 description 5
- 108020001507 fusion proteins Proteins 0.000 description 5
- 238000001415 gene therapy Methods 0.000 description 5
- 210000004602 germ cell Anatomy 0.000 description 5
- 239000006481 glucose medium Substances 0.000 description 5
- 101150048380 grp94 gene Proteins 0.000 description 5
- 230000002519 immonomodulatory effect Effects 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 238000003119 immunoblot Methods 0.000 description 5
- 238000002513 implantation Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 108020001756 ligand binding domains Proteins 0.000 description 5
- 230000035800 maturation Effects 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 238000001000 micrograph Methods 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 230000012846 protein folding Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 5
- 238000003757 reverse transcription PCR Methods 0.000 description 5
- 238000009738 saturating Methods 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 230000035939 shock Effects 0.000 description 5
- 210000000952 spleen Anatomy 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 230000002103 transcriptional effect Effects 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 241000972773 Aulopiformes Species 0.000 description 4
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 241000206602 Eukaryota Species 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 4
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 4
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 4
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 4
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 description 4
- 101001043564 Homo sapiens Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
- 108010052285 Membrane Proteins Proteins 0.000 description 4
- 101100011750 Mus musculus Hsp90b1 gene Proteins 0.000 description 4
- 108700008625 Reporter Genes Proteins 0.000 description 4
- 210000005221 acidic domain Anatomy 0.000 description 4
- 230000014102 antigen processing and presentation of exogenous peptide antigen via MHC class I Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 230000004094 calcium homeostasis Effects 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 238000001516 cell proliferation assay Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 210000000349 chromosome Anatomy 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 210000002308 embryonic cell Anatomy 0.000 description 4
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 4
- 229960002963 ganciclovir Drugs 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 230000008611 intercellular interaction Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 230000010311 mammalian development Effects 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000003938 response to stress Effects 0.000 description 4
- 102000029752 retinol binding Human genes 0.000 description 4
- 108091000053 retinol binding Proteins 0.000 description 4
- 235000019515 salmon Nutrition 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000002741 site-directed mutagenesis Methods 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 210000004988 splenocyte Anatomy 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 230000003827 upregulation Effects 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- JJIXGGRYEUBGKS-HLRRNAAZSA-N (2s)-2-[[2-[[(2s)-5-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoyl]amino]acetyl] Chemical compound C([C@@H](C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N)C(C)C)C1=CC=C(O)C=C1 JJIXGGRYEUBGKS-HLRRNAAZSA-N 0.000 description 3
- HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- 241000219194 Arabidopsis Species 0.000 description 3
- 108700031361 Brachyury Proteins 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 102100029968 Calreticulin Human genes 0.000 description 3
- 108090000549 Calreticulin Proteins 0.000 description 3
- 102000053642 Catalytic RNA Human genes 0.000 description 3
- 108090000994 Catalytic RNA Proteins 0.000 description 3
- 108700024394 Exon Proteins 0.000 description 3
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 3
- 102000018697 Membrane Proteins Human genes 0.000 description 3
- 108010021466 Mutant Proteins Proteins 0.000 description 3
- 102000008300 Mutant Proteins Human genes 0.000 description 3
- 101710141454 Nucleoprotein Proteins 0.000 description 3
- 101150092239 OTX2 gene Proteins 0.000 description 3
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 3
- 238000012408 PCR amplification Methods 0.000 description 3
- 108010071690 Prealbumin Proteins 0.000 description 3
- 102100021923 Prolow-density lipoprotein receptor-related protein 1 Human genes 0.000 description 3
- 238000010240 RT-PCR analysis Methods 0.000 description 3
- 238000002105 Southern blotting Methods 0.000 description 3
- 108020004440 Thymidine kinase Proteins 0.000 description 3
- 102000004338 Transferrin Human genes 0.000 description 3
- 108090000901 Transferrin Proteins 0.000 description 3
- 108700019146 Transgenes Proteins 0.000 description 3
- 102000009190 Transthyretin Human genes 0.000 description 3
- 101000980463 Treponema pallidum (strain Nichols) Chaperonin GroEL Proteins 0.000 description 3
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000005094 computer simulation Methods 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 230000007123 defense Effects 0.000 description 3
- VWLWTJHKQHRTNC-UHFFFAOYSA-L dipotassium;8-anilino-5-(4-anilino-5-sulfonatonaphthalen-1-yl)naphthalene-1-sulfonate Chemical compound [K+].[K+].C=12C(S(=O)(=O)[O-])=CC=CC2=C(C=2C3=CC=CC(=C3C(NC=3C=CC=CC=3)=CC=2)S([O-])(=O)=O)C=CC=1NC1=CC=CC=C1 VWLWTJHKQHRTNC-UHFFFAOYSA-L 0.000 description 3
- 238000009510 drug design Methods 0.000 description 3
- 231100001129 embryonic lethality Toxicity 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000001502 gel electrophoresis Methods 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 3
- 108091070631 heat shock protein 90 family Proteins 0.000 description 3
- 102000040622 heat shock protein 90 family Human genes 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 230000015788 innate immune response Effects 0.000 description 3
- 238000011813 knockout mouse model Methods 0.000 description 3
- 231100000518 lethal Toxicity 0.000 description 3
- 230000001665 lethal effect Effects 0.000 description 3
- 230000021633 leukocyte mediated immunity Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 238000013507 mapping Methods 0.000 description 3
- 102000035118 modified proteins Human genes 0.000 description 3
- 108091005573 modified proteins Proteins 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 239000002751 oligonucleotide probe Substances 0.000 description 3
- 230000005305 organ development Effects 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000035935 pregnancy Effects 0.000 description 3
- 239000002987 primer (paints) Substances 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 108091092562 ribozyme Proteins 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000012581 transferrin Substances 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 238000002424 x-ray crystallography Methods 0.000 description 3
- JVJGCCBAOOWGEO-RUTPOYCXSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-4-amino-2-[[(2s,3s)-2-[[(2s,3s)-2-[[(2s)-2-azaniumyl-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-phenylpropanoyl]amino]-4-carboxylatobutanoyl]amino]-6-azaniumy Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=CC=C1 JVJGCCBAOOWGEO-RUTPOYCXSA-N 0.000 description 2
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 102100029470 Apolipoprotein E Human genes 0.000 description 2
- 101710095339 Apolipoprotein E Proteins 0.000 description 2
- 108010071619 Apolipoproteins Proteins 0.000 description 2
- 102000007592 Apolipoproteins Human genes 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 2
- 101710201246 Eomesodermin Proteins 0.000 description 2
- 108010003471 Fetal Proteins Proteins 0.000 description 2
- 102000004641 Fetal Proteins Human genes 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 101150007068 HSP81-1 gene Proteins 0.000 description 2
- 101150087422 HSP82 gene Proteins 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101150068639 Hnf4a gene Proteins 0.000 description 2
- 108700005087 Homeobox Genes Proteins 0.000 description 2
- 101001120082 Homo sapiens P2Y purinoceptor 13 Proteins 0.000 description 2
- 101150028525 Hsp83 gene Proteins 0.000 description 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 101150097504 LHX1 gene Proteins 0.000 description 2
- 102100021926 Low-density lipoprotein receptor-related protein 5 Human genes 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 101150021503 Mesd gene Proteins 0.000 description 2
- 101000812646 Mus musculus Endoplasmin Proteins 0.000 description 2
- JADDQZYHOWSFJD-FLNNQWSLSA-N N-ethyl-5'-carboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 JADDQZYHOWSFJD-FLNNQWSLSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 102100026168 P2Y purinoceptor 13 Human genes 0.000 description 2
- 238000010222 PCR analysis Methods 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 101800001357 Potential peptide Proteins 0.000 description 2
- 102400000745 Potential peptide Human genes 0.000 description 2
- 102100037089 Protein disulfide-isomerase A4 Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 241000269370 Xenopus <genus> Species 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 210000001691 amnion Anatomy 0.000 description 2
- 210000000628 antibody-producing cell Anatomy 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 230000003190 augmentative effect Effects 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 210000001136 chorion Anatomy 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000007878 drug screening assay Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000000295 emission spectrum Methods 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 108010063267 endoplasmic reticulum glycoprotein p72 Proteins 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 230000009643 growth defect Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 101150099805 htpG gene Proteins 0.000 description 2
- 230000028996 humoral immune response Effects 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- 230000000984 immunochemical effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 239000002555 ionophore Substances 0.000 description 2
- 230000000236 ionophoric effect Effects 0.000 description 2
- 231100000225 lethality Toxicity 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 102000006240 membrane receptors Human genes 0.000 description 2
- 108020004084 membrane receptors Proteins 0.000 description 2
- 230000006609 metabolic stress Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 238000000302 molecular modelling Methods 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000001936 parietal effect Effects 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 239000011814 protection agent Substances 0.000 description 2
- 238000000164 protein isolation Methods 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 210000001995 reticulocyte Anatomy 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000037351 starvation Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 235000011178 triphosphate Nutrition 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 235000002374 tyrosine Nutrition 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 230000004906 unfolded protein response Effects 0.000 description 2
- 241001515965 unidentified phage Species 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 210000001325 yolk sac Anatomy 0.000 description 2
- XSDVNQZWTFDETM-ZETCQYMHSA-N (2s)-2-(ethoxycarbonylamino)-3-(1h-imidazol-5-yl)propanoic acid Chemical compound CCOC(=O)N[C@H](C(O)=O)CC1=CN=CN1 XSDVNQZWTFDETM-ZETCQYMHSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- 101150055869 25 gene Proteins 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 108010052946 Activin Receptors Proteins 0.000 description 1
- 102000018918 Activin Receptors Human genes 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102100033312 Alpha-2-macroglobulin Human genes 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102000018720 Basic Helix-Loop-Helix Transcription Factors Human genes 0.000 description 1
- 108010027344 Basic Helix-Loop-Helix Transcription Factors Proteins 0.000 description 1
- 108091005753 BiP proteins Proteins 0.000 description 1
- 102000001893 Bone Morphogenetic Protein Receptors Human genes 0.000 description 1
- 108010040422 Bone Morphogenetic Protein Receptors Proteins 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 101000693922 Bos taurus Albumin Proteins 0.000 description 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 1
- 101100279441 Caenorhabditis elegans egg-5 gene Proteins 0.000 description 1
- 101100512078 Caenorhabditis elegans lys-1 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000004612 Calcium-Transporting ATPases Human genes 0.000 description 1
- 108010017954 Calcium-Transporting ATPases Proteins 0.000 description 1
- 102100021868 Calnexin Human genes 0.000 description 1
- 108010056891 Calnexin Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 206010068051 Chimerism Diseases 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 238000011537 Coomassie blue staining Methods 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 101100125027 Dictyostelium discoideum mhsp70 gene Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 101710204837 Envelope small membrane protein Proteins 0.000 description 1
- 102100030751 Eomesodermin homolog Human genes 0.000 description 1
- 241000160765 Erebia ligea Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 102000008857 Ferritin Human genes 0.000 description 1
- 108050000784 Ferritin Proteins 0.000 description 1
- 238000008416 Ferritin Methods 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 206010071602 Genetic polymorphism Diseases 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101150031823 HSP70 gene Proteins 0.000 description 1
- 102100032510 Heat shock protein HSP 90-beta Human genes 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 102220622566 Hematopoietic prostaglandin D synthase_D93N_mutation Human genes 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- 102000009331 Homeodomain Proteins Human genes 0.000 description 1
- 108010048671 Homeodomain Proteins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000799189 Homo sapiens Activin receptor type-1B Proteins 0.000 description 1
- 101001016856 Homo sapiens Heat shock protein HSP 90-beta Proteins 0.000 description 1
- 101001043594 Homo sapiens Low-density lipoprotein receptor-related protein 5 Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 241000341655 Human papillomavirus type 16 Species 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 241000712431 Influenza A virus Species 0.000 description 1
- 101710203526 Integrase Proteins 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 102000012411 Intermediate Filament Proteins Human genes 0.000 description 1
- 108010061998 Intermediate Filament Proteins Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 101000988090 Leishmania donovani Heat shock protein 83 Proteins 0.000 description 1
- 108010015167 Low Density Lipoprotein Receptor-Related Protein-5 Proteins 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 101710145006 Lysis protein Proteins 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
- 102000000440 Melanoma-associated antigen Human genes 0.000 description 1
- 108050008953 Melanoma-associated antigen Proteins 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 1
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 1
- 108010084498 Myosin Heavy Chains Proteins 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 102000002584 Octamer Transcription Factor-3 Human genes 0.000 description 1
- 108010068425 Octamer Transcription Factor-3 Proteins 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 102100037968 Ribonuclease inhibitor Human genes 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 101710106714 Shutoff protein Proteins 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 208000035199 Tetraploidy Diseases 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 108010060804 Toll-Like Receptor 4 Proteins 0.000 description 1
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 1
- 108010060888 Toll-like receptor 2 Proteins 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 102100026773 Unconventional myosin-Ia Human genes 0.000 description 1
- 101710135389 Unconventional myosin-Ia Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 101100074799 Xenopus laevis lhx1 gene Proteins 0.000 description 1
- 241000235033 Zygosaccharomyces rouxii Species 0.000 description 1
- YVNQAIFQFWTPLQ-UHFFFAOYSA-O [4-[[4-(4-ethoxyanilino)phenyl]-[4-[ethyl-[(3-sulfophenyl)methyl]amino]-2-methylphenyl]methylidene]-3-methylcyclohexa-2,5-dien-1-ylidene]-ethyl-[(3-sulfophenyl)methyl]azanium Chemical compound C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C(=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S(O)(=O)=O)C)C=2C(=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S(O)(=O)=O)C)C=C1 YVNQAIFQFWTPLQ-UHFFFAOYSA-O 0.000 description 1
- 108700025690 abl Genes Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 230000008848 allosteric regulation Effects 0.000 description 1
- 210000001132 alveolar macrophage Anatomy 0.000 description 1
- 238000003277 amino acid sequence analysis Methods 0.000 description 1
- 238000012443 analytical study Methods 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000007503 antigenic stimulation Effects 0.000 description 1
- 229940076005 apoptosis modulator Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 108010028263 bacteriophage T3 RNA polymerase Proteins 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Chemical group OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 102000028861 calmodulin binding Human genes 0.000 description 1
- 108091000084 calmodulin binding Proteins 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000033081 cell fate specification Effects 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 230000007960 cellular response to stress Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 210000002777 columnar cell Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000009402 cross-breeding Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 210000003785 decidua Anatomy 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 101150052825 dnaK gene Proteins 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000010318 early mammalian development Effects 0.000 description 1
- 210000001705 ectoderm cell Anatomy 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 210000002242 embryoid body Anatomy 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 239000012645 endogenous antigen Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 238000012248 genetic selection Methods 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 210000002980 germ line cell Anatomy 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960004198 guanidine Drugs 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- 210000004837 gut-associated lymphoid tissue Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000009067 heart development Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 239000004030 hiv protease inhibitor Substances 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000000899 immune system response Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000010921 in-depth analysis Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000009349 indirect transmission Effects 0.000 description 1
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 1
- 229960004657 indocyanine green Drugs 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000010436 membrane biogenesis Effects 0.000 description 1
- 230000034217 membrane fusion Effects 0.000 description 1
- 210000001704 mesoblast Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001360 methionine group Chemical class N[C@@H](CCSC)C(=O)* 0.000 description 1
- 238000012737 microarray-based gene expression Methods 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 238000012243 multiplex automated genomic engineering Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000001087 myotubule Anatomy 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000001020 neural plate Anatomy 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- VOFUROIFQGPCGE-UHFFFAOYSA-N nile red Chemical compound C1=CC=C2C3=NC4=CC=C(N(CC)CC)C=C4OC3=CC(=O)C2=C1 VOFUROIFQGPCGE-UHFFFAOYSA-N 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 108010082406 peptide permease Proteins 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical group [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 238000003322 phosphorimaging Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 230000009894 physiological stress Effects 0.000 description 1
- 230000028742 placenta development Effects 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 108010024226 placental ribonuclease inhibitor Proteins 0.000 description 1
- 230000008121 plant development Effects 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 210000001586 pre-b-lymphocyte Anatomy 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 238000003498 protein array Methods 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000011536 re-plating Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108010078070 scavenger receptors Proteins 0.000 description 1
- 102000014452 scavenger receptors Human genes 0.000 description 1
- 239000013606 secretion vector Substances 0.000 description 1
- 238000011896 sensitive detection Methods 0.000 description 1
- PCMORTLOPMLEFB-ONEGZZNKSA-N sinapic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC(OC)=C1O PCMORTLOPMLEFB-ONEGZZNKSA-N 0.000 description 1
- PCMORTLOPMLEFB-UHFFFAOYSA-N sinapinic acid Natural products COC1=CC(C=CC(O)=O)=CC(OC)=C1O PCMORTLOPMLEFB-UHFFFAOYSA-N 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000000672 surface-enhanced laser desorption--ionisation Methods 0.000 description 1
- 238000003239 susceptibility assay Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 description 1
- 229950007866 tanespimycin Drugs 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 125000000341 threoninyl group Chemical class [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- 239000000717 tumor promoter Substances 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 238000003158 yeast two-hybrid assay Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0276—Knock-out vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/385—Haptens or antigens, bound to carriers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4614—Monocytes; Macrophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4615—Dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464476—Heat shock proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0331—Animal model for proliferative diseases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6043—Heat shock proteins
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Environmental Sciences (AREA)
- Wood Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
Applications Claiming Priority (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US46972303P | 2003-05-12 | 2003-05-12 | |
US60/469,723 | 2003-05-12 | ||
US47814903P | 2003-06-12 | 2003-06-12 | |
US47799003P | 2003-06-12 | 2003-06-12 | |
US60/477,990 | 2003-06-12 | ||
US60/478,149 | 2003-06-12 | ||
US56636304P | 2004-04-28 | 2004-04-28 | |
US56636204P | 2004-04-28 | 2004-04-28 | |
US60/566,363 | 2004-04-28 | ||
US60/566,362 | 2004-04-28 | ||
PCT/US2004/015120 WO2004101766A2 (en) | 2003-05-12 | 2004-05-12 | Grp94-based compositions and methods of use thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
AU2004239338A1 true AU2004239338A1 (en) | 2004-11-25 |
Family
ID=33459327
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU2004239338A Abandoned AU2004239338A1 (en) | 2003-05-12 | 2004-05-12 | GRP94-based compositions and methods of use thereof |
Country Status (6)
Country | Link |
---|---|
US (1) | US7589174B2 (de) |
EP (1) | EP1625141A4 (de) |
JP (1) | JP2007504840A (de) |
AU (1) | AU2004239338A1 (de) |
CA (1) | CA2525385A1 (de) |
WO (1) | WO2004101766A2 (de) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080199486A1 (en) * | 2003-05-12 | 2008-08-21 | Yair Argon | Grp94-based compositions and methods of use thereof |
US20060029610A1 (en) * | 2003-05-12 | 2006-02-09 | Yair Argon | GRP94-based compositions and methods of use thereof |
EP1789805B1 (de) * | 2004-07-14 | 2010-09-15 | The Regents of The University of California | Biomarker für den frühzeitigen nachweis von ovarialkarzinom |
US9488655B2 (en) * | 2004-07-14 | 2016-11-08 | The Regents Of The University Of California | Biomarkers for detection of early- and late-stage endometrial cancer |
US9487575B2 (en) | 2004-07-14 | 2016-11-08 | The Regents Of The University Of California | Compositions and methods for treatment of gynecologic cancers |
CN100419078C (zh) * | 2005-11-18 | 2008-09-17 | 李川源 | 一种表达糖调节蛋白的方法及其应用 |
EP2268298A1 (de) | 2008-03-13 | 2011-01-05 | Compugen Ltd. | Neue von gp96 abgeleitete peptide |
WO2013033260A1 (en) | 2011-08-29 | 2013-03-07 | The Regents Of The University Of California | Use of hdl-related molecules to treat and prevent proinflammatory conditions |
ES2769543T3 (es) * | 2012-09-28 | 2020-06-26 | Us Gov Sec Navy | Calibración de nanoestructuras plasmónicas individuales para la biodetección cuantitativa |
US20210277052A1 (en) * | 2020-03-03 | 2021-09-09 | Hauptman-Woodward Medical Research Institute | Recombinant grp94 chaperones and methods of using the same to modulate glycosylation in fusion proteins |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5188964A (en) | 1990-04-12 | 1993-02-23 | Board Of Regents, The University Of Texas System | Method and kit for the prognostication of breast cancer patient via heat shock/stress protein determination |
US6017540A (en) | 1997-02-07 | 2000-01-25 | Fordham University | Prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases with heat shock/stress protein-peptide complexes |
US20020039583A1 (en) * | 1999-09-30 | 2002-04-04 | Subjeck John R. | Stress protein compositions and methods for prevention and treatment of cancer and infectious disease |
US7235649B2 (en) * | 2000-03-24 | 2007-06-26 | Duke University | Isolated GRP94 ligand binding domain polypeptide and nucleic acid encoding same, and screening methods employing same |
AU2001247759A1 (en) | 2000-03-24 | 2001-10-08 | Duke University | Characterization of grp94-ligand interactions and purification, screening, and therapeutic methods relating thereto |
AU2001277961A1 (en) | 2000-08-07 | 2002-02-18 | Antigenics, Llc | Compositions comprising heat shock proteins or alpha(2)macroglobulin, antigenic molecules and saponins, and methods of use thereof |
AU2002217866A1 (en) | 2000-11-06 | 2002-05-15 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Geldanamycin derivatives useful for the treatment of cancer |
US20060029610A1 (en) | 2003-05-12 | 2006-02-09 | Yair Argon | GRP94-based compositions and methods of use thereof |
-
2004
- 2004-05-12 US US10/844,711 patent/US7589174B2/en active Active
- 2004-05-12 WO PCT/US2004/015120 patent/WO2004101766A2/en active Application Filing
- 2004-05-12 EP EP04752200A patent/EP1625141A4/de not_active Withdrawn
- 2004-05-12 CA CA002525385A patent/CA2525385A1/en not_active Abandoned
- 2004-05-12 JP JP2006533063A patent/JP2007504840A/ja active Pending
- 2004-05-12 AU AU2004239338A patent/AU2004239338A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP1625141A2 (de) | 2006-02-15 |
WO2004101766A3 (en) | 2005-03-24 |
US20050063982A1 (en) | 2005-03-24 |
US7589174B2 (en) | 2009-09-15 |
CA2525385A1 (en) | 2004-11-25 |
JP2007504840A (ja) | 2007-03-08 |
EP1625141A4 (de) | 2007-07-04 |
WO2004101766A2 (en) | 2004-11-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Zukerberg et al. | Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth | |
JP2020062014A (ja) | ポリペプチド、核酸およびその使用 | |
US20130236404A2 (en) | Substances and compositions for enhancing dna repair and methods of use | |
JP5114418B2 (ja) | 細胞死を抑制する又は細胞増殖を高めるための方法及び組成物 | |
US7589174B2 (en) | GRP94-based compositions and methods of use thereof | |
US20080199486A1 (en) | Grp94-based compositions and methods of use thereof | |
JP2023093533A (ja) | 放射線または放射線療法によって引き起こされた放射線誘発性バイスタンダ効果を防止および治療するための組成物および方法 | |
US20100144543A1 (en) | Epigenetic silencing of tumor suppressor genes | |
US7052889B2 (en) | Mammalian SUV39H2 proteins and isolated DNA molecules encoding them | |
JP2003508011A (ja) | ヒトfez1遺伝子である新規ガン抑制遺伝子に関する組成物、キットおよび方法 | |
ES2279629T3 (es) | Nueva colectina. | |
US20060029610A1 (en) | GRP94-based compositions and methods of use thereof | |
JP2009536526A (ja) | Zpaポリペプチドに関連する方法および組成物 | |
US20100015654A1 (en) | Negative regulation of NK cell functions by EAT-2, a sap-related adaptor expressed in innate immune cells | |
JP2003535596A (ja) | Suv39h2メチルトランスフェラーゼのモジュレーターのスクリーニング法 | |
US20090162848A1 (en) | Noxin, a novel stress-induced gene involved in cell cycle and apoptosis | |
US6740751B2 (en) | Methods and compositions for stabilizing microtubules and intermediate filaments in striated muscle cells | |
WO2000010602A9 (en) | Lats knock-out animal models and their uses | |
US20070298026A1 (en) | Methods for Identifying Treatment and Inducing Infertility Using Smc1-Beta | |
Angelats et al. | Cubitus interruptus acts to specify naked cuticle in the trunk of Drosophila embryos | |
Gupta et al. | Actins and Myosins | |
Vivegananthan | Molecular and genetic analysis of the sex-determining proteins FEM-1 and FEM-3 | |
JP2003144168A (ja) | 核外移行機能又は核−細胞質間移行機能を有する細胞周期関連タンパク質 | |
WO2005060364A2 (en) | Spatial for altering cell proliferation | |
JP2005287418A (ja) | 細胞殺傷性と細胞死防御性とを併せもつペプチド |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |